Yi S J, Gifford A N, Johnson K M
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Eur J Pharmacol. 1991 Jun 25;199(2):185-9. doi: 10.1016/0014-2999(91)90456-z.
The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca(2+)-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 muM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 muM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 muM, respectively. The effect of 5-HT on Ca(2+)-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.
研究了血清素（5-羟色胺，5-HT）对预先装载[3H]多巴胺（[3H]DA）的纹状体突触体中氚释放的影响。5-HT以浓度依赖性方式刺激氚的自发释放和Ca(2+)诱发的流出。非选择性5-HT激动剂d-麦角酸二乙胺未模拟出这种效应。此外，5 μM 5-HT的刺激作用不受选择性5-HT3受体拮抗剂MDL-72222和GR-38032F的影响。另一方面，可卡因和选择性DA摄取抑制剂诺米芬辛分别以0.2和0.09 μM的IC50值完全拮抗5 μM 5-HT对自发氚流出的作用。5-HT对Ca(2+)诱发的氚流出的作用也被这些DA摄取抑制剂阻断，尽管所需浓度略高。这些数据支持这样一种假说，即5-HT通过一种涉及5-HT转运到多巴胺能终末的机制诱导纹状体神经终末释放DA，而不是像在纹状体切片中观察到的5-HT效应所提出的那样通过激活5-HT3受体。
